Bibliographic details of the publications numerically referred to in this specification are collected at the end of the description.
The exploitation of recombinant DNA technology in the treatment and prophylaxis of disease conditions requires a level of understanding of regulatory mechanisms involved in gene expression commensurate with the complexity of the genetic disorder to be treated. This is particularly the case for the myriad of regulatory molecules involved in cell fate determination and tissue differentiation during developmental processes.
One important class of regulatory molecules are members of the basic helix-loop-helix (bHLH) family of transcription factor proteins which are involved in cellular proliferation and differentiation during developmental processes including haemopoiesis, myogenesis and neurogenesis (1, 2). These proteins share a common sequence motif consisting of a basic (b) region and an adjacent helix-loop-helix (HLH) structure. The b region is important for DNA binding while the HLH domain mediates dimerization (3, 4).
Myogenic-specific bHLH proteins are involved in the activation of genes required for proper vertebrate development. bHLH proteins MyoD, Myf-5, Myf-4 and myogenin interact with class I HLH proteins.
bHLH proteins are also involved in antigen dependent B-cell differentiation. ABF-1 is a bHLH protein capable of binding with the product of the E2A gene to the E2 box elements of the b region of ABF-1.
In work leading up to the present invention, the inventors sought to identify other bHLH genes. The inventors have identified a gene having nucleotide sequence similarity to ABF-1 but which is involved in myogenesis.